Kryazhimskiy_eta...
- 格式：pdf
- 大小：196.60 KB
- 文档页数：2
3 JUNE 2011 VOL 332 SCIENCE www.sciencemag.org
1160PERSPECTIVES
Propagating bacteria in a lab for thousands of genera-tions may seem tedious, or even irrelevant, to most evolution-ary biologists. Nonetheless, such experiments provide an opportunity to deduce quantitative principles of evolution and directly test them in controlled environments. Combined with modern sequencing technolo-gies, as well as theory, recent micro-bial experiments have suggested a critical role for genetic interactions among mutations, called epistasis, in determining the pace of evolution. Two papers in this issue, by Khan et al. on page 1193 ( 1) and Chou et al. ( 2) on page 1190, present precise experimental measurements of these epistatic interactions.Microbial evolution experiments in a simple, constant environment reveal a characteristic pattern: At fi rst, a population rapidly acquires beneficial mutations, but then adaptation progressively slows so that thousands of generations pass between subsequent benefi cial substitutions ( 3). Unexpected outcomes, however, can and do occur even in these simple experimental conditions. Populations evolve a dramatically elevated mutation rate ( 4), discover rare phe-notypic innovations ( 5), or diverge into dis-tinct lineages that either coexist ( 6) or com-pete vigorously as each strain races to acquire more adaptive mutations ( 7). Recent theory suggests that a common cause underlies all these phenomena: the structure of epistatic interactions among mutations.Epistasis describes how the fi tness conse-quence of a mutation depends on the status of the rest of the genome. In one extreme exam-ple, called sign epistasis, a mutation may be benefi cial if it arises on one genetic back-ground, but detrimental on another. Although interactions among genes may seem an obvi-ous fact of biology, the myriad possible forms of epistasis have made it diffi cult to formu-late predictive evolutionary models or to infer such interactions from empirical data. Nev-ertheless, epistasis is at the heart of classi-cal theories, such as the evolution of sex ( 8), and also of modern concepts such as robust-ness and evolvability (a population’s ability to evolve) ( 9). Moreover, recent theoretical work ( 10) suggests that the overall dynami-cal pattern of adaptation observed in long-term microbial experiments can be explained by a prevalence of what is called antagonistic epistasis, in which benefi cial mutations con-fer less benefi t in combination than they do individually.To quantify epistasis among beneficial mutations and to test these theoretical predic-tions, both Khan et al. and Chou et al. exam-ined the initial substitutions that occurred in populations of bacteria adapting in the labo-ratory. The researchers identifi ed the hand-ful of mutations across the genome that had substituted in an evolved strain, and then con-structed intermediate strains containing com-binations of these mutations. By measuring the fi tness benefi ts conferred by these muta-tions, individually and in combination, the researchers were able to directly quantify the extent and form of epistasis (see the fi gure).Both studies found a predominance of antagonistic epistasis, which impeded the rate of ongoing adaptation relative to a null model of independent mutational effects. Chou et al. further interpreted the prevalence of antagonistic epistasis in terms of meta-bolic costs and benefi ts. The concordance of results from the two studies is noteworthy, especially because Khan et al. analyzed Esch-erichia coli populations [from the long-term experiments of Lenski ( 3)], whereas Chou et al. studied an engineered strain of Methylo-bacterium extorquens. The remarkable preci-sion with which both studies quantifi ed epis-tasis among benefi cial mutations was made possible only by leveraging whole-genome sequencing combined with the ability to reconstruct mutational combinations and assay them in the same environment in which the mutations fi rst arose.The view of epistasis across a genome that emerges from this work contrasts sharply In Evolution, the Sum Is Less than Its PartsEVOLUTION
SergeyKryazhimskiy,1,2 Jeremy A. Draghi ,1 Joshua B. Plotkin 1 Laboratory experiments with bacteria shed light on how epistatic interactions infl uence the pace of evolution.
Ancestor strainAdapted strain
Reconstruct intermediatesEvolves in lab
Diminishing returnsFitness Wab
Fitness WbFitness Wa
1stmutation2ndmutation3rdmutationFitnessAntagonistic epistasisWab < Wa • WbAntagonistic epistasis. Bacteria adapt to a laboratory environment by acquiring benefi cial mutations. Khan et al. and Chou et al. identifi ed the mutations that accrued in an adapted strain, and measured their fi tness benefi ts (growth advantage relative to the ancestor). The mutations conferred smaller marginal benefi ts in combination than they did individually. This antagonistic epistasis causes progressively slower rates of adaptation over time.
